Physicochemical Properties of Carbamic Acid Derivatives

Background: Derivatives of carbamic acid are conveniently prepared by reactions of alcohols with carbamoyl (R₂NCOCl) chlorides or isocyanates and sometimes by reactions of amines with alkyl chloroformate (ROCOCl) esters. Such derivatives are important in biosynthesis, human pharmacotherapy, polymer chemistry, systemic insecticide synthesis, and as wood and paint preservatives. However, carbamoyl chlorides and chloroformates, in general, are listed as federal hazardous pollutants due to the observation of chronic health effects following occupational exposure. Hence, it is important to comprehend any correlations between their chemical structure, aqueous solvent effects, and chemical reactivity. This undergraduate project analyzes the solvent effects on two N,N-disubstituted (dialkyl and dialkenyl) carbamoyl chlorides and two substituted (2-fluoro and 2-benzyloxy) ethyl chloroformate (EtOCOCl) esters. The substrates analyzed are: N,N-diisopropyl carbamoyl chloride (1), N,N-diallyl carbamoyl chloride (2), 2-fluoroethyl chloroformate (3), and 2-benzyloxyethyl chloroformate (4) Methods: The kinetic studies were completed utilizing common experimental techniques. For fast reactions, a Kinet^®using micro-ohm sensitive probes is used to measure conductance from the production of acid during solvolysis. For the slow reactions, we used acid-base titrations using lacmoid as an indicator and sodium methoxide as the base. Along with the solvolytic effects, thermodynamic effects on the carbamoyl chlorides are also analyzed. Results: Correlation analyses using linear free energy relationships (LFERs) are used to predict and explain substrate reactivity and mechanistic pathways in solvents of differing nucleophilicity and ionizing ability. Conclusions:  Statistical analysis of the kinetic data-sets suggests that the rate of reaction in R₂NCOCl is directly dependent upon the intensive electron release from the R groups, whereas, there is a dependence on the electron withdrawing character of the substituent in the 2-position in EtOCOCl.  Acknowledgements: Research reported in this poster was supported by a National Science Foundation (NSF) Experimental Program to Stimulate Competitive Research (Delaware-EPSCoR) grant EPS-0814251, and an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number 8 P20 GM103446-14. Victor also received a NASA/Delaware Space Grant (NNG05GO92H) Undergraduate Tuition Scholarship, and a Cannon Scholarship from an NSF S-STEM program (NSF-DUE 1355554).